Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer.
Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events in lung adenocarcinoma. We found that 2369 of the 17 800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the existence and overexpression of a novel variant of P16 transcribed from the CDKN2A locus. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy.
Xi
Liqiang
L
Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.
Feber
Andrew
A
Gupta
Vanita
V
Wu
Maoxin
M
Bergemann
Andrew D
AD
Landreneau
Rodney J
RJ
Litle
Virginia R
VR
Pennathur
Arjun
A
Luketich
James D
JD
Godfrey
Tony E
TE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017398:Alternative Splicing; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000737:chemistry; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
D015703:Antigens, CD; C069847:CD66 antigens; C512197:CDH3 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D019941:Cyclin-Dependent Kinase Inhibitor p16; C072312:ERG protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG